The necessity of healthcare supply chain resilience for crisis preparedness.

Prior to and during the COVID-19 pandemic, Canadian provincial health systems and governments did not sufficiently consider healthcare supply chain in their crisis preparedness plans, leading to an exposed and vulnerable healthcare system. There have been many opportunities to learn from past Canadian and global crises, which have emphasized the importance of healthcare supply chain resilience in providing essential care to patients; however, considerations of healthcare supply chain resilience remain a significant gap in preparedness planning. Illustrated through the Canadian response to COVID-19 pandemic, this article will explore how healthcare supply chain resilience should be a necessary consideration in any crisis preparedness plans. Further, without this consideration of healthcare supply chain resilience, it is the person (the patient and healthcare worker), and especially vulnerable populations, that are most put at risk in the event of a future crisis.

Dietary nitrate supplementation enhances heavy load carriage performance in military cadets.

PURPOSE: To determine the effects of dietary nitrate (NO3-) supplementation on physiological responses, cognitive function, and performance during heavy load carriage in military cadets. METHODS: Ten healthy males (81.0 ± 6.5 kg; 180.0 ± 4.5 cm; 56.2 ± 3.7 ml·kg·min-1 VO2max) consumed 140 mL·d-1 of beetroot juice (BRJ; 12.8 mmol NO3-) or placebo (PL) for six d preceding an exercise trial, which consisted of 45 min of load carriage (55% body mass) at 4.83 km·h-1 and 1.5% grade, followed by a 1.6-km time-trial (TT) at 4% grade. Gas exchange, heart rate, and perceptual responses were assessed during constant-load exercise and the TT. Cognitive function was assessed immediately prior to, during, and post-exercise via the psychomotor vigilance test (PVT). RESULTS: Post-TT HR (188 ± 7.1 vs. 185 ± 7.4; d = 0.40; p = 0.03), mean tidal volume (2.15 ± 0.27 vs. 2.04 ± 0.23; p = 0.02; d = 0.47), and performance (770.9 ± 78.2 s vs. 809.8 ± 61.4 s; p = 0.03; d = 0.63) were increased during the TT with BRJ versus PL. There were no effects of BRJ on constant-load gas exchange or perceptual responses, and cognitive function was unchanged at all time points. CONCLUSION: BRJ supplementation improves heavy load carriage performance in military cadets possibly as a result of attenuated respiratory muscle fatigue, rather than enhanced exercise economy.

Standardization of EUS imaging and reporting in high-risk individuals of pancreatic adenocarcinoma: consensus statement of the Pancreatic Cancer Early Detection Consortium.

BACKGROUND AND AIMS: Pancreatic ductal adenocarcinoma is an aggressive disease most often diagnosed after local progression or metastatic dissemination, precluding resection and resulting in a high mortality rate. For individuals with elevated personal risk of the development of pancreatic cancer, EUS is a frequently used advanced imaging and diagnostic modality. However, variability in the expertise and definition of EUS findings exists among gastroenterologists, as well as a lack of standardized reporting of relevant findings at the time of examination. Adoption of standardized EUS reporting, using a universally accepted and agreed on terminology, is needed. METHODS: A consensus statement designed to create a standardized reporting template was authored by a multidisciplinary group of experts in pancreatic diseases that includes gastroenterologists, radiologists, surgeons, oncologists, and geneticists. This statement was developed using a modified Delphi process as part of the Pancreatic Cancer Early Detection Consortium, and >75% agreement was required to reach consensus. RESULTS: We identified reporting elements and present standardized reporting templates for EUS indications, procedural data, EUS image capture, and descriptors of findings, tissue sampling, and postprocedural assessment of adequacy. CONCLUSIONS: Adoption of this standardized EUS reporting template should improve consistency in clinical decision-making for individuals with elevated risk of pancreatic cancer by providing complete and accurate reporting of pancreatic abnormalities. Standardization will also help to facilitate research and clinical trial design by using clearly defined and consistent imaging descriptions, thus allowing for comparison of results across different centers.

Supply chain capacity to respond to COVID-19 in Newfoundland and Labrador: An integrated leadership strategy.

This provincial case study, one of seven conducted as part of a national research program on healthcare supply chain management during COVID-19, focuses on Newfoundland and Labrador (NL). Faced with the destabilization of its traditional supply chain, NL leveraged an existing centralized healthcare supply chain structure to organize its supply chain response to the pandemic. To overcome product shortages, health leaders collaborated with their local business community and industries to source and procure personal protective equipment and create domestic manufacturing capacity for critical supplies. The healthcare supply chain response in NL demonstrates the value of a highly integrated and centralized healthcare supply chain management strategy. It also makes clear the value of a diversified healthcare supply chain, one which draws on local manufacturing capacity to create a domestic source of critical supplies and overcome shortages from global suppliers.

Supply chain integration as a strategy to strengthen pandemic responsiveness in Nova Scotia.

This provincial case study, one of seven conducted as part of a national research program on healthcare supply chain management during COVID-19, focuses on Nova Scotia. During the first wave of the pandemic, Nova Scotia faced the massive destabilization of its traditional supply channels and had to grapple with role clarity and communication in its emergency response structure. Nova Scotia was able to centralize its pandemic sourcing, procurement, and management efforts to its provincial health authority. Healthcare supply chain teams were able to rapidly modify their sourcing and procurement processes in order to compensate for the destabilization of their standard supply channels and assume responsibility for the province-wide management and distribution of pandemic supplies. The Nova Scotia case findings make clear both the value of a centralized and dedicated healthcare supply chain response-that integrates all provincial care delivery organizations-and the diversification of the healthcare supply chain.

The Emerging Features of Healthcare Supply Chain Resilience: Learning from a Pandemic.

The COVID-19 pandemic exposed significant fragilities in the configuration of global healthcare supply chains. This was felt acutely by citizens, patients and healthcare workers across Canada. As demand for critical medical products surged in Canada, and globally, provincial healthcare supply chain teams worked to rapidly stabilize their supply chains. These efforts indicate the emerging features of healthcare supply chain resilience. Results suggest that there are five emerging features: (1) redundancy of supply inventory; (2) diversification of suppliers across geographies; (3) maturity of digital infrastructure to create transparency; (4) proactivity; and (5) equity of distribution to protect the lives of all.

Carbohydrate supplementation: a critical review of recent innovations.

PURPOSE: To critically examine the research on novel supplements and strategies designed to enhance carbohydrate delivery and/or availability. METHODS: Narrative review. RESULTS: Available data would suggest that there are varying levels of effectiveness based on the supplement/supplementation strategy in question and mechanism of action. Novel carbohydrate supplements including multiple transportable carbohydrate (MTC), modified carbohydrate (MC), and hydrogels (HGEL) have been generally effective at modifying gastric emptying and/or intestinal absorption. Moreover, these effects often correlate with altered fuel utilization patterns and/or glycogen storage. Nevertheless, performance effects differ widely based on supplement and study design. MTC consistently enhances performance, but the magnitude of the effect is yet to be fully elucidated. MC and HGEL seem unlikely to be beneficial when compared to supplementation strategies that align with current sport nutrition recommendations. Combining carbohydrate with other ergogenic substances may, in some cases, result in additive or synergistic effects on metabolism and/or performance; however, data are often lacking and results vary based on the quantity, timing, and inter-individual responses to different treatments. Altering dietary carbohydrate intake likely influences absorption, oxidation, and and/or storage of acutely ingested carbohydrate, but how this affects the ergogenicity of carbohydrate is still mostly unknown. CONCLUSIONS: In conclusion, novel carbohydrate supplements and strategies alter carbohydrate delivery through various mechanisms. However, more research is needed to determine if/when interventions are ergogenic based on different contexts, populations, and applications.

The fibers of the circular junction of the linea alba in normal adult anatomy.

The linea alba (LA) is known to be useful to surgeons for making surgical incisions. Laparoscopic entry into the peritoneal cavity using the open technique may involve identification of a point just above or below the umbilicus where the peritoneum is fused to the LA. This anatomical site is found through superficial dissection to expose the junction between the umbilical stalk (US) and the LA, where distinct fibers seem to form a unique ligament-like structure in normal adult anatomy. This point, in fact, is part of a circular fibrous structure that exists almost like a ring around the remnant US. It is formed by the fusion of oblique and transverse fibers of the LA with circular fibers from proliferation of an encircling band of compact mesoderm to close a patent umbilical ring. We describe and name this anatomical landmark as junctio circularis alba or the "circular junction of the LA" as encountered in normal adult human anatomy. We believe this is crucial for describing key surgical procedures at this site to aid effective surgical training and reduce iatrogenic complications from laparoscopic port site entries.

An unusual cause of stridor.

A 12-month-old infant was referred with a 6-week history of recurrent admissions with worsening stridor. On each previous admission, the stridor responded well, but transiently, to oral dexamethasone. At this presentation, he required high-dependency unit care with high flow oxygen due to marked increased work of breathing.He was born at term, previously well, and up to date with immunisations. There was no significant family history. There were no smokers and two cats at home.He was afebrile with moderate subcostal recession and tracheal tug. On auscultation, breath sounds were normal with transmitted sounds of inspiratory and expiratory stridor. The rest of his examination was normal.He commenced dexamethasone 0.15 µg/kg three times a day, which was weaned as his clinical status improved.Blood tests showed total white cell count 9 x 10ˆ9/L, CRP <1 mg/L, lactate dehydrogenase level and blood film normal. Chest radiograph showed left lung hyperexpansion and apparent right-sided bronchial narrowing (figure 1). Flexible nasendoscopy was unremarkable. Microlaryngoscopy and bronchoscopy showed external airway compression at the level of the carina (figure 2). CT thorax demonstrated a non-enhancing mediastinal mass extrinsic to the airway, approximately 3cmx2.5cmx1.5cm, compressing the carina and main-stem bronchi (figure 3).

Paediatric tonsillectomy in England: A cohort study of clinical practice and outcomes using Hospital Episode Statistics data (2008-2019).

OBJECTIVES: To assess the safety of paediatric tonsillectomy procedures conducted in NHS hospitals in England between 2008 and 2019. DESIGN: Retrospective observational cohort study using Hospital Episode Statistics (HES) data. SETTING: Acute NHS trusts in England conducting paediatric tonsillectomy procedures. PARTICIPANTS: Children (≤16 years old) undergoing bilateral tonsillectomy. MAIN OUTCOME MEASURES: Number of tonsillectomies performed per year by procedural method. In-hospital complications including return to theatre for arrest of haemorrhage. Readmission within 28 days, including those for pain, haemorrhage and surgical arrest of haemorrhage. Long-term outcomes: all-cause mortality, revision tonsillectomy. RESULTS: A total of 318 453 paediatric tonsillectomies were performed from 2008 to 2019:278,772 dissection (87.5%) and 39 681 coblation (12.5%). The proportion of tonsillectomy performed using coblation increased from 7% in 2008/9 to 27% in 2018/9. Five patients died in hospital (including 4 due to respiratory complications). In-hospital complications occurred in 4202 children (1.3%), with the most frequent being haemorrhage. Within 28 days of tonsillectomy, 28 170 patients (8.8%) were readmitted and 7 deaths occurred. Readmission rates for haemorrhage and pain have increased since 2008. The proportion of children undergoing revision tonsillectomy procedures within 5 years following coblation tonsillectomy (1.4%) was approximately double that of dissection (0.6%). CONCLUSIONS: Clinical practice of paediatric tonsillectomy has changed in England over the past 11 years. The overall mortality rate associated with the procedure is 0.0037%. Differences in outcomes have been identified for different procedural methods. However, routine administrative data are limited in differentiating procedural detail (eg we are unable to differentiate intra or extra-capsular techniques from current clinical coding of tonsillectomy procedures). Therefore, prospective national data collection or more granular clinical coding is essential to capture relative outcomes of the different tonsillectomy methods and techniques being used in the NHS.

COVID-19, Workforce Autonomy and the Health Supply Chain.

During the COVID-19 pandemic, the rapid surge in demand for critical supplies and public health efforts needed to guard against virus transmission have placed enormous pressure on health systems worldwide. These pressures and the uncertainty they have created have impacted the health workforce in a substantial way. This paper examines the relationship between health supply chain capacity and the impact of the COVID-19 pandemic on Canada's health workforce. The findings of this research also highlight the impact of the pandemic on health workers, specifically the relationship between the health supply chain and the autonomy of the health workforce.

An Evidence-Based Strategy to Scale Vaccination in Canada.

Provincial health systems have been challenged by the surge in healthcare demands caused by the COVID-19 pandemic; the COVID-19 vaccine rollout across the country has further added to these challenges. A successful vaccination campaign is widely viewed as the only way to overcome the COVID-19 pandemic, placing greater urgency on the need for a rapid vaccination strategy. In this paper, we present emerging findings, from a national research study, that document the key challenges faced by current vaccine rollout strategies, which include procurement and leadership strategies, citizen engagement and limitations in supply chain capacity. These findings are used to inform a scalable vaccine strategy comprising collaborative leadership, mobilization of an integrated workforce and a digitally enabled supply chain strategy. The goal of vaccinating the entire Canadian population in the next few months can be achieved when supported by such a strategy.

Key Characteristics of a Fragile Healthcare Supply Chain: Learning from a Pandemic.

The COVID-19 pandemic has highlighted the many challenges that provincial health systems have experienced while scaling health services to protect Canadians from viral transmission and support care for those who get infected. Supply chain capacity makes it possible for health systems to deliver care and implement public health initiatives safely. In this paper, we present emerging findings from a national research study that documents the key features of the fragility of the health supply chain evident across the seven Canadian provinces. Results suggest that the fragility of the health supply chain contributes to substantive challenges across health systems, thus limiting or precluding proactive and comprehensive responses to pandemic management. These findings inform strategies to strengthen supply chain capacity and performance in order to enable health systems to effectively respond to pandemic events.

Prescribed fire and partial overstory removal alter an acorn-rodent conditional mutualism.

In eastern North America, oak (Quercus) regeneration failure has spurred management using silvicultural approaches better aligned with the autecology of oaks. In particular, shelterwood harvests can create favorable intermediate light conditions for oak establishment and prescribed fire is predicted (by the oak-fire hypothesis) to favor oak regeneration. These approaches substantially modify forest structure and may affect crucial trophic interactions including the conditional mutualism between oaks and granivorous rodents that scatterhoard acorns, which shifts along a continuum from antagonistic to mutualistic depending on external factors. We investigated how overwinter survival and dispersal of northern red oak (Quercus rubra) acorns were influenced by location within or outside of group shelterwood harvests (small canopy gaps created throughout an intact forest stand) with and without prescribed fire. We conducted two concurrent experiments to test (1) dispersal and survival of acorns presented on the forest floor and (2) acorn pilferage rates from caches that mimic squirrel scatterhoards in shelterwood gap/group interiors, edges, and the uncut forest matrix in burned and unburned forest stands. In both experiments, acorn survival was generally higher in burned than unburned stands. Acorn survival from forest floor presentations was higher in the unharvested forest matrix than harvest gap interiors; however, there was no effect of proximity to harvest gaps on survival of cached acorns. Survival of cached acorns was associated with understory vegetative cover (-), coarse woody debris cover (-), and distance to nearest tree (+), but uncorrelated with canopy cover above the cache. Our results suggest that reduced understory cover following prescribed fire may increase perceived habitat riskiness for granivores resulting in higher acorn survival up to 2 yr post-fire. These findings unify the oak-fire and oak-granivore conditional mutualism hypotheses, and suggest that the environmental conditions following prescribed fire and group shelterwood harvests may shift the oak-granivore conditional mutualism in a direction beneficial for oak regeneration.

Carbohydrate hydrogel beverage provides no additional cycling performance benefit versus carbohydrate alone.

PURPOSE: This study examined the effects of a novel maltodextrin-fructose hydrogel supplement (MF-H) on cycling performance and gastrointestinal distress symptoms. METHODS: Nine endurance-trained male cyclists (age = 26.1 ± 6.6, mass = 80.9 ± 10.4 kg, VO2max = 55.5 ± 3.6 mL·kg·min-1) completed three experimental trials consisting of a 98-min varied-intensity cycling protocol followed by a performance test of ten consecutive sprint intervals. In a cross-over design, subjects consumed 250 mL of a treatment beverage every 15 min of cycling. Treatments consisted of 78 g·hr-1 of either (a) MF-H, (b) isocaloric maltodextrin-fructose (ratio-matched 2:1; MF), and (c) isocaloric maltodextrin only (MD). RESULTS: There were no differences in average sprint power between treatments (MF-H, 284 ± 51 W; MF, 281 ± 46 W; and MD, 277 ± 48 W), or power output for any individual sprint. Subjective ratings of gastrointestinal distress symptoms (nausea, fullness, and abdominal cramping) increased significantly over time during the cycling trials, but few individuals exceeded moderate levels in any trial with no systematic differences in gastrointestinal discomfort symptoms observed between treatments. CONCLUSIONS: In conclusion, ingestion of a maltodextrin/fructose hydrogel beverage during high-intensity cycling does not improve gastrointestinal comfort or performance compared to MF or MD beverages.

A bispecific antibody strategy to target multiple type 2 cytokines in asthma.

BACKGROUND: Asthma is a chronic inflammatory airway disease in which innate and adaptive immune cells act together to cause eosinophilic inflammation, goblet cell metaplasia (GCM), and bronchial hyperreactivity (BHR). In clinical trials using biologicals against IL-4 receptor (IL-4R) α or IL-5, only a subset of patients with moderate-to-severe asthma responded favorably, suggesting that distinct pathophysiologic mechanisms are at play in subgroups of patients called endotypes. However, the effect of multiple cytokine blockade using bispecific antibodies has not been tested. OBJECTIVE: We sought to target simultaneously the IL-4, IL-13, and IL-5 signaling pathways with a novel IL-4Rα/IL-5-bispecific antibody in a murine house dust mite (HDM) model of asthma. METHODS: Two mAbs neutralizing IL-4Rα and IL-5 were generated by using a llama-based antibody platform. Their heavy and light chains were then cotransfected in mammalian cells, resulting in a heterogeneous antibody mixture from which the bispecific antibody was isolated by using a dual anti-idiotypic purification process. C57BL/6J mice were finally sensitized and challenged to HDM extracts and treated during challenge with the antibodies. RESULTS: We successfully generated and characterized the monospecific and bispecific antibodies targeting IL-4Rα and IL-5. The monospecific antibodies could suppress eosinophilia, IgE synthesis, or both, whereas only the IL-4Rα/IL-5-bispecific antibody and the combination of monospecific antibodies additionally inhibited GCM and BHR. CONCLUSION: Type 2 cytokines act synergistically to cause GCM and BHR in HDM-exposed mice. These preclinical results show the feasibility of generating bispecific antibodies that target multiple cytokine signaling pathways as superior inhibitors of asthma features, including the difficult-to-treat GCM.

Systems biology definition of the core proteome of metabolism and expression is consistent with high-throughput data.

Finding the minimal set of gene functions needed to sustain life is of both fundamental and practical importance. Minimal gene lists have been proposed by using comparative genomics-based core proteome definitions. A definition of a core proteome that is supported by empirical data, is understood at the systems-level, and provides a basis for computing essential cell functions is lacking. Here, we use a systems biology-based genome-scale model of metabolism and expression to define a functional core proteome consisting of 356 gene products, accounting for 44% of the Escherichia coli proteome by mass based on proteomics data. This systems biology core proteome includes 212 genes not found in previous comparative genomics-based core proteome definitions, accounts for 65% of known essential genes in E. coli, and has 78% gene function overlap with minimal genomes (Buchnera aphidicola and Mycoplasma genitalium). Based on transcriptomics data across environmental and genetic backgrounds, the systems biology core proteome is significantly enriched in nondifferentially expressed genes and depleted in differentially expressed genes. Compared with the noncore, core gene expression levels are also similar across genetic backgrounds (two times higher Spearman rank correlation) and exhibit significantly more complex transcriptional and posttranscriptional regulatory features (40% more transcription start sites per gene, 22% longer 5'UTR). Thus, genome-scale systems biology approaches rigorously identify a functional core proteome needed to support growth. This framework, validated by using high-throughput datasets, facilitates a mechanistic understanding of systems-level core proteome function through in silico models; it de facto defines a paleome.

One duct, two orifices, no names! the anatomy of the biliary cystic duct.

The biliary cystic duct (CD) connects the gallbladder to the extra-hepatic bile duct, and the point at which it does this delineates the division between the common hepatic duct and the common bile duct. Its clinical relevance in disease, and importance during interventions relating to the gallbladder mean that its normal and variant anatomy has been described extensively in literature. However, an aspect not yet fully described includes naming of its two orifices on either end. This is highly relevant for surgical, endoscopic, and percutaneous procedures. We describe these as encountered in normal CD and biliary tree anatomy. We believe this is crucial for interventions relating to the gallbladder and the biliary tree, including prevention of iatrogenic injury. Clin. Anat. 31:422-423, 2018. © 2018 Wiley Periodicals, Inc.

Functional diversity response to hardwood forest management varies across taxa and spatial scales.

Contemporary forest management offers a trade-off between the potential positive effects of habitat heterogeneity on biodiversity, and the potential harm to mature forest communities caused by habitat loss and perforation of the forest canopy. While the response of taxonomic diversity to forest management has received a great deal of scrutiny, the response of functional diversity is largely unexplored. However, functional diversity may represent a more direct link between biodiversity and ecosystem function. To examine how forest management affects diversity at multiple spatial scales, we analyzed a long-term data set that captured changes in taxonomic and functional diversity of moths (Lepidoptera), longhorned beetles (Coleoptera: Cerambycidae), and breeding birds in response to contemporary silvicultural systems in oak-hickory hardwood forests. We used these data sets to address the following questions: how do even- and uneven-aged silvicultural systems affect taxonomic and functional diversity at the scale of managed landscapes compared to the individual harvested and unharvested forest patches that comprise the landscapes, and how do these silvicultural systems affect the functional similarity of assemblages at the scale of managed landscapes and patches? Due to increased heterogeneity within landscapes, we expected even-aged silviculture to increase and uneven-aged silviculture to decrease functional diversity at the landscape level regardless of impacts at the patch level. Functional diversity responses were taxon-specific with respect to the direction of change and time since harvest. Responses were also consistent across patch and landscape levels within each taxon. Moth assemblage species richness, functional richness, and functional divergence were negatively affected by harvesting, with stronger effects resulting from uneven-aged than even-aged management. Longhorned beetle assemblages exhibited a peak in species richness two years after harvesting, while functional diversity metrics did not differ between harvested and unharvested patches and managed landscapes. The species and functional richness of breeding bird assemblages increased in response to harvesting with more persistent effects in uneven- than in even-aged managed landscapes. For moth and bird assemblages, species turnover was driven by species with more extreme trait combinations. Our study highlights the variability of multi-taxon functional diversity in response to forest management across multiple spatial scales.

solveME: fast and reliable solution of nonlinear ME models.

BACKGROUND: Genome-scale models of metabolism and macromolecular expression (ME) significantly expand the scope and predictive capabilities of constraint-based modeling. ME models present considerable computational challenges: they are much (>30 times) larger than corresponding metabolic reconstructions (M models), are multiscale, and growth maximization is a nonlinear programming (NLP) problem, mainly due to macromolecule dilution constraints. RESULTS: Here, we address these computational challenges. We develop a fast and numerically reliable solution method for growth maximization in ME models using a quad-precision NLP solver (Quad MINOS). Our method was up to 45 % faster than binary search for six significant digits in growth rate. We also develop a fast, quad-precision flux variability analysis that is accelerated (up to 60× speedup) via solver warm-starts. Finally, we employ the tools developed to investigate growth-coupled succinate overproduction, accounting for proteome constraints. CONCLUSIONS: Just as genome-scale metabolic reconstructions have become an invaluable tool for computational and systems biologists, we anticipate that these fast and numerically reliable ME solution methods will accelerate the wide-spread adoption of ME models for researchers in these fields.